Volumetric and MGMT parameters in glioblastoma patients: survival analysis.

Volumetric and MGMT parameters in glioblastoma patients: survival analysis.
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DOI:
10.1186/1471-2407-12-3
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发表时间:
2012-01-03
期刊:
影响因子:
3.8
通讯作者:
Fountzilas G
Fountzilas G
中科院分区:
医学2区
文献类型:
--
作者:
Iliadis G;Kotoula V;Chatzisotiriou A;Televantou D;Eleftheraki AG;Lambaki S;Misailidou D;Selviaridis P;Fountzilas G

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在这项研究中,通过基于计算机的应用程序评估了几个肿瘤相关的体积,并进行了生存分析,以评估术前和术后体积数据在胶质母细胞瘤患者中的预后意义。此外,MGMT(O 6-甲基鸟嘌呤甲基转移酶)相关参数与容量法进行了比较,以观察该分子在肿瘤发展中的可能相关性。我们前瞻性分析了65例胶质母细胞瘤(GBM)患者接受放疗伴随辅助替莫唑胺。为了进行容量测定,使用了术前和术后(放疗前)采集的T1和T2加权磁共振(MR)序列。术前测量肿瘤体积为坏死、强化和水肿(包括肿瘤),术后测量肿瘤体积为网状强化。年龄、性别、体力状态(PS)和手术类型也被纳入多变量分析。采用多重连接依赖性探针扩增法(MLPA)检测MGMT的启动子甲基化,采用真实的时间PCR检测MGMT的RNA表达,采用免疫组化检测MGMT的蛋白表达。在多变量分析中,放疗前净增强肿瘤对总生存期(OS)(p = 0.023)和术前坏死对无进展生存期(PFS)(p = 0.030)有负面影响。此外,多因素分析证实了PS在患者PFS和OS中的重要性。在13/23(43.5%)的可评估肿瘤中观察到MGMT启动子甲基化;仅在3/13的甲基化肿瘤中观察到完全甲基化。高MGMT蛋白阳性率(> 20%阳性肿瘤细胞核)与术前肿瘤坏死呈负相关(p = 0.021)。我们的研究结果表明,体积参数可能有一个显着的作用,GBM患者的预后。此外,容量测定法不仅可以帮助改善结果的预测,而且可以通过识别治疗失败的高风险患者来改善结果本身,从而为这些患者寻求替代治疗。在这个小系列中,MGMT蛋白与侵袭性较低的肿瘤特征相关。
In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore, volumetry could help not only to improve the prediction of outcome but also the outcome itself by identifying patients at high risk of treatment failure and, thus, seek alternative treatment for these patients. In this small series, MGMT protein was associated with less aggressive tumor characteristics.
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